慢性疼痛发病机制复杂，仍缺乏有效的治疗手段。近年发现circRNA与疼痛发生关系密切，但其调控机制仍不清楚。预试验发现，神经病理疼痛下：1）小鼠脊髓circRNA-Kat6b下调显著，过表达circRNA-Kat6b能减轻疼痛；2）circRNA-Kat6b基因上游存在超级增强子SE，且活性降低；体外报告表明SE能增强基因表达；SE活性相关蛋白Spt6表达下降；3）miRNA-26a表达增加，能结合到circRNA-Kat6b，下调miRNA-26a能降低痛敏；4）钾离子通道Kcnk1的mRNA存在miRNA-26a结合位点，miRNA-26a能调控Kcnk1报告基因活性。因此，本项目拟以神经病理性疼痛小鼠为模型，从整体、细胞和分子水平阐明受超级增强子调控的circRNA-Kat6b通过miRNA-26a/Kcnk1对脊髓突触可塑性和痛行为的调节机制，以期为慢性疼痛治疗提供新思路。

Chronic pain is a frequently-occurring and refractory disease and lacks specific effective drugs in treatment. Recent findings suggest that circRNA, a new regulatory mechanism of gene expression, plays an important role in the development and maintenance of chronic pain. In the preliminary experiment, the following critical results had been found. Firstly, circRNA-Kat6b was significantly decreased in spinal cord of chronic constrictive injury (CCI)-induced chronic neuropathic pain mice. Overexpression of circRNA-Kat6b alleviated the pain sensitivity to the thermal and mechanical stimulus. Secondly, ChIP-Seq result showed that one super enhancer (SE) existed in the upstream of circRNA-Kat6b gene, and the spinal SE activity was reduced under the condition of neuropathic pain. The SE enhanced the expression of report gene. The expression of Spt6, a histone chaperone involved in the modulation of the SE activity, was decreased after CCI surgery. Thirdly, miRNA-26a was increased in the spinal cord of CCI mice, and could bind to the circRNA-Kat6b. Knockdown of spinal miRNA-26a attenuated the pain. Finally, Kcnk1 was a predictive target of miRNA-26a, overexpression of miRNA-26a inhibited the activity of reporter, which was inserted by Kcnk1 fragment bound by miRNA-26a; contrarily, downregulation of miRNA-26a increased the activity of Kcnk1-reporter. Taken together, the purpose of this study is to investigate whether circRNA-Kat6b regulated by super enhancer is involved in the process of chronic neuropathic pain via targeting miRNA-26a/Kcnk1 at the spinal cord level. This study will reveal a new functional regulatory epigenetic mechanism underlying neuropathic pain, which will provide a possible target for the development of analgesic drugs.